The Comparative Bioavailability of a Generic and the Innovator Fluconazole Preparations in Healthy Thai Volunteers
SUPANIMIT TEEKACHUNHATEAN, M.D.*, NOPPAMAS ROJANASTEIN, M.D.*, MALEEYA MANOROT, M.D.*, CHAICHAN SANGDEE, Ph.D. (Pharmacol)*, AMPHA WAN APISARIYAKUL, Ph.D. (Pharmacol)*, UDOMCHAI AJAYUTPHOKIN, M.S. (Pharmacol)*
Affiliation : * Clinical Pharmacology Division, Department of Pharmacology. Faculty of Medicine. Chiang Mai University. Chiang Mai 50200, Thailand.
Abstract We studied the pharmacokinetics and compared the oral bioavailability of the "genenc (Biozole®, Biolab Company, Thailand) and the "innovator" (Diflucan®, Pfizer Incorporation, U.S.A.) fluconazole preparations in 12 healthy Thai volunteers. A 200 mg single oral dose of each preparation was given to the subjects in a randomized double-blind 2-period crossover design with 2 weeks washout period. Blood samples were collected just before and at 0.5. I, 2, 2.5, 3, 4, 24, 48, 56 and 72 hours after drug administration. Serum fluconazole concentra- tions were determined by using high performance liquid chromatography. Individual concen- tration-time profiles and the pharmacokinetic parameters were analyzed by the noncom- partmental pharmacokinetic method [TOPFIT, a pharmacokinetic data analysis program]. The pharmacokinetic parameters (T max• Cmax• V d• Cl) of fluconazole in Thai healthy volunteers were comparable to those values observed in Caucasian subjects. The relative bioavailability of the generic Biozole® was 102.38 ± 9.79 per cent of Diflucan®. The means and 90 per cent confidence intervals (90% Cl) of the [Biozole®/ Diflucan®] ratio of AUC0-72• AUCO-inf and Cmax were 1.02 (0.98-1.06), 0.99 (0.95-1.03) and 1.13 ( 1.03-1.25), respectively. These values were well within the acceptable bioequivalence ranges of 0.8-1.25 proposed by the US FDA. The means and 90 per cent CI of Tmax differences [Biozole®- Diflucan®] were -0.46 [(-1.03)- (0.12)]. This value was outside the stipulated bioequivalence range of± 0.41 h (± 20% of the T max of the reference formulation). Nevertheless, the T max difference was not expected to be related to the differences in safety and efficacy of the drug. Hence, Biozole® and Diflucan® were bioequivalent with respect to the extent of absorption (AUC), al'd the Cmax• and could be used interchangeably.
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